急性臭氧暴露对血清氧化脂质谱的影响:基于随机交叉对照试验OA

[Background]Previous studies suggest that ozone exposure may affect cardiovascular health by inducing oxidative stress.However,most prior research has focused on individual oxylipins,lacked rigorous control for confounding factors,and failed to systematically explore changes across the comprehensive oxylipin profile. [Objective]To investigate the effects of short-term ozone exposure on serum oxylipin profile. [Methods]This study performed a targeted serum oxylipidomic analysis using samples from a previously executed controlled human ozone exposure trial.Thirty-two eligible participants were randomly assigned to receive 2 h exposures to ozone or filtered air(FA),in random sequence,separated by a two-week washout period.Venous blood was collected within 2 h post-exposure.Ultra-performance liquid chromatography-tandem mass spectrometry was used for the separation and detection of serum oxylipins.Orthogonal partial least squares discriminant analysis(OPLS-DA)and linear mixed-ef-fects(LME)models were used to evaluate the differences in oxylipin levels between the two exposures.Differentially expressed oxylipins were identified using a variable importance in projection(VIP)score>1 and a false discovery rate(FDR)<0.05. [Results]A total of 29 participants completed both exposure sessions,yielding 58 serum samples.Among the 97 oxylipins quantified,11 were significantly altered following ozone exposure compared to FA,with results remaining robust in sensitivity analyses.Specifically,ozone exposure significantly increased the concentration of the oxidative stress biomarker 2,3-dinor-8-iso-PGF2α by 91.93%(95%CI:46.73%,151.07%).Conversely,ozone exposure significantly decreased the levels of 10 other oxylipins by 22.42%to 55.57%.These included 5-isoPGF2VI,downstream metabolites of the cyclooxygenase(COX)signaling pathway(11-keto-thromboxane B2,11-keto-TXB2;and 11β-prostaglandin F2α,11β-PGF2α),and lipoxygenase(LOX)pathway products[tetranor-12(S)-hydroxyeicosatetraenoic acid,tetranor-12(S)-HETE;8(S)-hydroxyeicosatrienoic acid,8(S)-HETrE;14(S)-hydroxy docosahexaenoic acid,14(S)-HDHA;17-hydroxy docosahexaenoic acid,17-HDHA;4-hydroxy docosahexaenoic acid,4-HDHA;10-hydroxy docosahexaenoic acid,10-HDHA;and 12-hydroxyeicosapentaenoic acid,12-HEPE]. [Conclusion]Short-term ozone exposure significantly alters the serum oxylipin profile.These metabolic shifts suggest that ozone induces oxidative stress and subsequent lipid peroxidation,while concurrently inhibiting the COX and LOX signaling pathways,thereby weakening the body's pro-resolving capacity.